Role of nitric oxide-related inhibition in intestinal function: relation to vasoactive intestinal polypeptide

Abstract

This study examined the role of nitric oxide (NO) in tonic inhibition of motor activity in isolated, perfused canine ileal segments. Brief addition of N omega-nitro-L-arginine methyl ester (L-NAME) to the perfusate caused, after a delay, a concentration-dependent persistent increase in tonic and phasic activity of circular muscle. This increased motor activity was prevented or reversed by addition of L- but not D-arginine to the perfusate. Removal of Ca2+ or addition of 10(-7) M omega-conotoxin (GVIA) to the perfusate markedly reduced this response. The motor activity induced by L-NAME was accompanied by loss of distal inhibition and enhanced excitation to low-frequency field stimulation. L-NAME infusion significantly reduced tonic vasoactive intestinal polypeptide (VIP) output, sodium nitroprusside increased VIP output, but L-arginine infusion did not restore VIP output. Atropine (10(-7) M) and/or hexamethonium (10(-4) M) reduced the motor response to L-NAME by 75%. Atropine reduced and hexamethonium nearly abolished VIP output. We conclude that there is tonic Ca(2+)-dependent NO output from perfused intestinal segments dependent on nerves with N-Ca channels, that NO acts to inhibit muscle directly and by inhibiting release of excitatory mediators, and that this output is the primary inhibitory determinant of contractile activity.

Local, exendin-(9—39)-insensitive, site of action of GLP-1 in canine ileum

“…When TTX (10-20 g) was infused and responses to EFS were abolished, persistent phasic and tonic activity ensued as previously described (12,35). GLP-1 had no effect on this activity in concentrations through 3 ϫ 10 Ϫ7 M (data not shown), indicating that it had no effect on myogenic activity, consistent with its lack of inhibitory effect on responses to intraarterial acetylcholine.…”

“…GLP-1 had no effect on this activity in concentrations through 3 ϫ 10 Ϫ7 M (data not shown), indicating that it had no effect on myogenic activity, consistent with its lack of inhibitory effect on responses to intraarterial acetylcholine. Perfusion of L-NNA (10 Ϫ4 M) also induced persistent tonic and phasic activity, but responses to excitatory stimulation of proximal enteric nerves were preserved, as previously described (12). GLP-1 had a reduced inhibitory effect on these responses, suggesting that nitric oxide release mediated its effects in part (Fig.…”

Location and Function of VPAC1, VPAC2 and NPR-C Receptors in VIP-Induced Vasodilation of Porcine Basilar Arteries

“…This was initially proposed after the observation that electrically induced VIP release from guinea-pig stomach smooth muscle strips was reduced by L-NAME (Grider et al, 1992). L-NAME-mediated reductions in VIP release have also been reported in rat and rabbit gastric fundus smooth muscle preparations and in isolated perfused dog ileal segments (Daniel et al, 1994;Jin et al, 1996;Chakder and Rattan, 1998). In addition, NO donors have been used to enhance VIP release from rat intestinal synaptosomal preparations, showing that VIP release is stimulated by NO (Allescher et al, 1996;Kurjak et al, 2001).…”

The Whole Shebang: The Gastrointestinal Tract,Escherichia coliEnterotoxins and Secretion

“…A VIP antagonist partially prevented STa induced secretion demonstrating that VIPergic neurons and NO synthase containing neurons coexist in the ENS (Llewellyn-Smith et al, 1992). In addition, NO may release VIP from nerve terminals (Allescher et al, 1996) and VIP may cause release of NO (Daniel et al, 1994). Thus, we may speculate that NO and VIP interact to induce secretion by STa.…”